Biology subjects

Montoya, M. M.

Publications and source records attributed to Montoya, M. M..

3 recordsLinked to original sources

bioRxiv2025

Structure-Based Optimization of Pathogen Signal Sequences for Enhanced Antigen Expression in Humans for Vaccine Designs

Signal peptides (SPs) are short amino acid sequences found at the N-terminus of nascent polypeptides, which serve critical roles in trafficking, folding, and post-translational processing of mature proteins. Many sequence-based computational methods have been developed to predict and design optimal SPs for protein secretion in human cells. In this work, we introduce a structure-based workflow for identifying SPs and their regions, aiming to optimize SPs for protein secretion in human cells. Structural modeling of the SPs in complex with human signal recognition particle 54 kDa (SRP54), combined with hydrophobicity plots of the SPs and identification of the cleavage motif, can be used to detect SPs and SP regions. Afterwards, LigandMPNN is applied to redesign the SPs based on their structural complexes with SRP54. We employ our workflow to optimize the bacterial Yersinia pestis F1 SP, Lassa virus glycoprotein (GP) SP, and Venezuelan equine encephalitis virus (VEEV) E3 envelope protein for protein secretion in human cells to serve as vaccine candidates. By comparing the redesigned SPs with the original SPs, we propose that the binding affinity of SPs to SRP54 serve as the most important molecular determinant in the activity of the SPs. Notably, our experiments confirm that the structurally optimized SPs can express the Y. pestis F1 protein, Lassa GP, and VEEV GP in human cells. Overall, we demonstrate that structural modeling can serve as a valuable tool to predict the SPs and SP regions for vaccine antigens, predict whether the SPs can express mature proteins in humans, and optimize the SPs for the expression of mature proteins in humans.

biophysics↗

bioRxiv2025

Human pulvinar stimulation engages select cortical pathways in epilepsy

The pulvinar has been proposed as an effective neuromodulation target for patients with posterior quadrant and temporal epilepsies. However, the pulvinar has a large tissue volume, multiple subnuclei, and widespread cortical connections. It remains unknown whether electrical stimulation of distinct pulvinar subregions affects the temporal, occipital, and parietal areas differently. To address this gap, we delivered single-pulse electrical stimulation to the pulvinar and measured the resulting brain stimulation evoked potentials in twelve patients undergoing stereotactic EEG for drug-resistant epilepsy. Brain stimulation evoked potentials were parameterized across the occipital, temporal and parietal cortex. Stimulation of the lateral pulvinar elicited significant brain stimulation evoked potentials in striate and extrastriate areas that diminish as stimulation shifts towards the medial pulvinar. Conversely, stimulation of the ventral aspect of the medial pulvinar produced significant lateral temporal evoked potentials, which diminish with lateral pulvinar stimulation. We also found that stimulation of the dorsomedial pulvinar evoked significant parietal responses with limited striate/extrastriate and lateral temporal responses. These results demonstrate that electrical stimulation of specific pulvinar subregions influences distinct occipital, parietal and lateral temporal areas. Selective targeting of pulvinar subregions to maximize seizure network engagement may be essential for individualized treatment of posterior quadrant and temporal epilepsies.

neuroscience↗

bioRxiv2024

Quantification of heterogeneity in human CD8+ T cell responses to vaccine antigens: an HLA-guided perspective

Vaccines have historically played a pivotal role in controlling epidemics. Effective vaccines for viruses causing significant human disease, e.g., Ebola, Lassa fever, or Crimean Congo hemorrhagic fever virus, would be invaluable to public health strategies and counter-measure development missions. Here, we propose coverage metrics to quantify vaccine-induced CD8+T cell-mediated immune protection, as well as metrics to characterize immuno-dominant epitopes, in light of human genetic heterogeneity and viral evolution. Proof-of-principle of our approach and methods will be demonstrated for Ebola virus, SARS-CoV-2, and Burkholderia pseudomallei (vaccine) proteins.

immunology↗